FDA’s First Substantiation Guidance for a Conventional Food

FDA’s issuance of a draft guidance for industry titled Substantiation for Structure/Function Claims Made in Infant Formula Labels and Labeling marks the first issuance of a guidance that addresses structure/function (SF) claim substantiation for a conventional food. As FDA explains in the guidance, the agency regards SF claims for conventional foods to be narrower in scope than SF claims for dietary supplements because the former derive from the FDCA’s definition of “drug” and case law interpreting that definition – and should therefore “derive from the product’s character as a food.” Notwithstanding that narrower scope, the agency “intends to apply the ‘competent and reliable evidence’ standard for the substantiation of infant formula claims in a manner that is consistent with FTC’s and FDA’s approach for the substantiation of dietary supplement claims.” As flagged by the title of the guidance, FDA can be expected to apply the competent and reliable evidence standard not just to claims featured on a label, but also those featured on other materials that the agency views as falling under the broad umbrella of labeling.

Although the guidance is directed to infant formula – a product category subject to especially close regulatory scrutiny – the guidance should be reviewed by any marketer of conventional food. The guidance sets forth an analytical framework that will be familiar to those who track FDA and FTC’s approach to substantiation of other types of health-related claims. The guidance signals a preference for at least two “independent, well-conducted studies.” Further, in determining whether a claim is adequately substantiated, the guidance recommends “the use of a systematic evidence-based review process for evaluating the strength of the evidence.” The guidance describes the steps involved in that type of evaluation, and points to the agency’s approach to evaluating health claims as one of several examples of that approach.

As described in the guidance, an evidence-based review gives preference to well-conducted feeding intervention studies as the “most direct evidence for a cause-and-effect relationship.” Other types of studies “can provide supportive evidence.” Seriously flawed studies should be weeded out (e.g., those that don’t comply with subject protection requirements, target a different population, fail to use “recognized and accepted” endpoints, and/or lack adequate statistical power). Also deserving of exclusion are studies that fail to meet certain quality criteria. Then, the totality of evidence should be evaluated, with sensitivity to the fact that statistically significant differences “may not be clinically significant,” and with an eye toward whether there exist conflicting results that demand a plausible explanation. In the end, the question of “whether the totality of the evidence reaches the substantiation standard of competent and reliable scientific evidence” should turn on the following factors listed in the guidance:

What are the individual study’s strengths and weaknesses? For example, consider the quality of the study and the peer review.

If multiple studies exist, do the studies that have the highest quality suggest a particular outcome?

If multiple studies exist, what do most studies suggest or find? Does the totality of the evidence agree with the claim(s)?

Do other study designs that are limited in their usefulness to substantiate a structure/function claim in infant formula labeling provide additional supportive evidence for a claim?

Comments on the guidance should be submitted by November 8.

FDA issued another guidance (this one in final form) directed to labeling of infant formula generally. That guidance appears to have been motivated in part by the agency’s concern over different products bearing “the same or similar statements of identity,” and “increased use of nutrient content claims that render a product misbranded.” The guidance discusses why a statement of identity such as “Infant Formula” might not be adequate for a “Soy-Based Infant Formula Powder,” or a “High Protein (3.5g protein per 100 calories) Milk-Based Infant Formula Powder for Premature and Low Birth Weight Infants.” The guidance also reminds industry that the range of nutrient content claims permitted for infant formula is limited, and that health claims and qualified health claims must conform to conditions established by the agency.